1. Field of the Invention
This invention relates to a cartridge for storing a plurality of chemical analysis film chips each in a warped or curled state and having a reagent layer containing a reagent whose optical density changes through a chemical reaction, an immunoreaction or the like with a specific biochemical component contained in a sample liquid such as blood or urine. This invention further relates to a method of and a device for taking out the chemical analysis film chips from the cartridge one by one.
2. Description of the Prior Art
Quantitative or qualitative analysis of a specific component in a sample liquid is a common operation carried out various industrial fields. Especially, quantitative analysis of a chemical component or a solid component contained in body fluid such as blood or urine is very important in the field of clinical biochemistry.
There has been put into practice a "dry-to-the-touch" chemical analysis slide with which a specific component contained in a sample liquid can be quantitatively analyzed through a droplet of the sample liquid applied to the slide by spotting. See Japanese Patent Publication No. 53(1978)-21677, U.S. Pat. No. 3,992,158, Japanese Unexamined Patent Publication No. 55(1980)-164356, U.S. Pat. No. 4,292,272 or the like. When such a dry chemical analysis slide is used, the sample liquid can be analyzed more easily and more quickly than when the conventional wet analysis method is used, and accordingly the dry chemical analysis slide is very convenient for medical facilities, laboratories and the like where lots of sample liquids have to be analyzed.
When chemical components or the like contained in a sample liquid is quantitatively analyzed using such a dry chemical analysis slide, a droplet of the sample liquid is applied to the slide and is held at a constant temperature for a predetermined time in an incubator so that coloring reaction occurs, and the optical density of the color formed by the coloring reaction is optically measured. That is, measuring light containing a wavelength which is pre-selected according to the combination of the component to be analyzed and the reagent contained in the reagent layer of the slide is projected onto the slide and the optical density of the slide is measured. Then the component to be analyzed is quantitatively analyzed on the basis of the optical density using a calibration curve, which represents the relation between the concentration of the biochemical component and the optical density.
The chemical analysis slide generally comprises a dry chemical analysis film chip and a plastic frame which holds the chemical analysis film chip flat to facilitate handling of the film chip during transfer. The chemical analysis film chip is generally composed of a support sheet of plastic or the like and a reagent layer and a spreading layer formed on the support sheet.
When biochemical analysis is effected using such chemical analysis slides, the chemical analysis slides should be smoothly supplied one by one in order to facilitate automated analysis.
There has been known a cartridge in which a stack of, for instance, about fifty chemical analysis slides are stored. See U.S. Pat. Nos. 4,151,931, 4,187,077, 4,190,420, 4,279,861 and the like.
In this cartridge, when the uppermost slide is pushed out of the cartridge by a push member, a lift member is inserted into the cartridge through the bottom of the cartridge to move upward the stack of the slides by a distance corresponding to the thickness of one slide. All the slides in the cartridge are taken out by repeating the steps.
Since a large number of the slides are consumed in a short time and accordingly a large cartridge is necessary, and moreover, there are required a plurality of cartridges the same as the biochemical substances to be analyzed in number, which results in increase in the size of the biochemical analysis apparatus.
Further, in the case of the chemical analysis slide, cost of the frame is high, which adds to cost of biochemical analysis.
Accordingly, we have proposed a dry chemical analysis element without frame. The chemical analysis element comprises a support sheet and a reagent layer and the like laminated on the support sheet and is not provided with a frame. This type of chemical analysis element will be referred to as "frameless chemical analysis film chip" or simply as "chemical analysis film chip", hereinbelow. Further we have proposed a cartridge for storing therein a stack of the frameless chemical analysis film chips. The cartridge has a box-like body which is provided with a first opening which is formed an upper portion of a side wall of the body and through which the uppermost chemical analysis film chip is only taken out and a second opening through which a means for holding the uppermost chemical analysis film chip and taking it out through the first opening is given access to the uppermost chemical analysis film chip. See Japanese Unexamined Patent Publication No. 4(1992)-5508 (corresponding to European Patent Publication No. 0555654A2).
The proposed cartridge for the frameless chemical analysis film chips can be substantially smaller than the conventional cartridge for the chemical analysis slides, whereby the overall size of the biochemical analysis apparatus can be miniaturized. Further the cost of the frame can be cut and the cost of biochemical analysis can be lowered.
However, use of the frameless chemical analysis film chip involves a problem that since the frameless chemical analysis film chips warp in a dry state, it is necessary to handle the chemical analysis film chips in an automated system taking into account the shape of the chemical analysis film chip in a dry state.
That is, though the reagent layer or reagent in a porous layer cannot initiate a reaction without water, it can initiate a reaction as soon as it absorbs water, which can adversely affect the result of the biochemical analysis. Accordingly, the chemical analysis film chips are stored in a dry atmosphere such as in a drying container (supplier) until they are to be applied with a sample liquid. In the dry state, the chemical analysis film chips are warped (curled or curved) into a roof tile-like shape, and the state (degree or shape) of warp substantially changes depending on the kind of the chemical analysis film chip, which is determined according to the item of measurement. Even if the kind of the chemical analysis film chips are the same, the state of warp can change from chip to chip.
Accordingly, the mechanism for taking out the chemical analysis film chips from the cartridge should be arranged so that the chemical analysis film chips in different states of warp can be surely taken out one by one.
In European Patent Publication No. 0064691A1, there is disclosed a technique for taking out from a container analytical elements for semi-quantitative analysis each comprising a reagent layer formed on a part of a support sheet. In the technique, a stack of the analytical elements is accommodated in the container, and the container is provided with an opening in the bottom thereof. A suction means is introduced into the container through the opening and attracts the lowermost element thereon under a suction force. Then the suction means is moved downward to pull out the element through the opening while resiliently deforming the element.
However when the technique is applied to the chemical analysis film chips, those having a small radius of curvature are apt to fall through the opening and when the opening is narrowed to prevent such chemical analysis film chips having a small radius of curvature from falling through the opening, then it becomes difficult to take out those having a large radius of curvature through the opening. Thus it is difficult to apply the technique to take out the chemical analysis film chips.
In Japanese Unexamined Patent Publication No. 4(1992)-16098 (corresponding to European Patent Publication No. 0555654A2), there is further disclosed a supplier for storing a plurality of frameless chemical analysis film chips in a dry state before application of sample liquid. The supplier is provided with a cartridge holding means for holding a plurality of cartridges and the cartridge holding means is driven by a drive mechanism such as an electric motor to bring a desired cartridge to a film takeout port formed in the supplier. A suction means is provided near the film takeout port and takes out the film chip from the cartridge positioned opposed to the film takeout port. That is, the suction means is movable between a predetermined attracting position and a retracted position away from the attracting position. The attracting position is where the suction means can precisely attract the center of the film chip in the cartridge opposed to the film takeout port under a suction force. The suction means is moved to the attracting position from the retracted position after a desired cartridge is moved to the position opposed to the film takeout portion and takes out the film chip while holding it under a suction force.
It is important that the cartridge is in a fixed position relative to the attracting position when it is positioned opposed to the film takeout port (this position will be referred to as "the film takeout position" hereinbelow) since otherwise the suction means cannot attract the film chip at a constant portion. If the portion at which the suction means attracts the film chip changes chip to chip, various troubles can be caused during subsequent handling of the film chip. For example, the sample liquid cannot be applied to the film chips in a constant position therein, or the film chip can be brought into contact with a wall of a cell in an incubator when it is inserted into the cell and the sample liquid on the film chip can contaminate the cell or the film chip can be broken on impact.
Though there have been made various attempts to precisely position the cartridge in the film takeout position relative to the attracting position by improving the precision of the cartridge holding means drive mechanism, it has been difficult to improve the precision of the cartridge holding means drive mechanism to such a level. Especially when the cartridge holding means is in the form of a cartridge receiving portion which is formed in a disk-like rotary body and is moved along a circular path unlike that disclosed in Japanese Unexamined Patent Publication No. 4(1992)-16098 (corresponding to European Patent Publication No. 0555654A2) where the cartridge holding means is moved along a linear path, it is very difficult to precisely position the cartridge in the circumferential direction of the rotary body though the cartridge can be substantially precisely positioned in the radial direction of the rotary body.